Fibromyalgia

FIBROMYALGIA

Leena Mathew, M.D. Director Pain Fellowship Associate Professor Department of Anesthesiology Columbia University disclosures

I have no conflicts of interest objectives

• Be able to accurately diagnose fibromyalgia

• Understand the pathomechanism of fibromyalgia

• Identify a multimodal treatment plan for patients with fibromyalgia. prevalence / epidemiology

Prevalence 2-8% 4 million fibromyalgia patients 9 1 : 2 1

$5945 annually per person 35-60 years old history classic criteria 1990

98% patients / 69% controls

Sensitivity 88.4% specificity 81 1% fibromyalgia impact questionnaire ( FIQ) • validated 10-item instrument • sensitivity 93.1% / specificity 91.7% • Assesses impact on function and effect of treatment

R. Bennett 2005 revised ACR 2010 criteria

Eliminated tender point exam

widespread pain Index 0-19 Symptom severity score 0-12 • Fatigue • Cognition • Un-refreshed sleep • Somatic symptoms

WPI≥ 7 and SSS≥ 5 WPI= 3-6 and SSS≥ 9 Sensitivity 86%, specificity 90% revised 2011 ACR criteria Physician estimate of somatic symptoms eliminated and expanded the SSS

0-31 FM symptom scale (FS)

 19 pain locations  6 self-reported symptoms- poor sleep, fatigue, poor cognition + headache, depression or abdominal pain

FS ≥ 13 best meets criteria (sensitivity 96% and specificity 91%) 2016 revision

• Generalized pain in 4 of 5 regions.

• Symptoms > 3 months.

• WPI ≥ 7 and SSS score ≥ 5 or WPI of 4–6 and SSS score ≥ 9.

• Diagnosis of fibromyalgia valid irrespective of other diagnoses symptoms

• Chronic widespread pain Anxiety 40% • Fatigue Depression 50% • Non restorative sleep Sleep 90% Fatigue 90% • Mood / cognitive Pain 100% disturbances. comorbidities

Depression / anxiety Fatigue, cognitive ds

Headache / migraines Allergies Temporomandibular ds Esophageal dysmotility IBS Low back pain Reactive airway

Idiopathic paresthesias Pelvic pain, cystitis

Adapted from Aaron LA et al , Arch Int Med 2000; 160:221-227 multidimensional pathology

Inflammator Neurological Genetic Pain matrix y 1.Oxidative stress, 1, Aberrant transmission 1. 26% prevalence in 1° 1.Decreased binding of mitochondrial relatives vs. 19% in µ- receptors in r-ACC damage cause a 2 Serotonin/ NE and  EAA unrelated subjects inflammatory state. 2. Volume change in 4.  epidermal nerve fiber density 2. Multiple genetic amygdala, hippocampus, 2.Inflammatory polymorphisms effect PFC, ACC and insula. cytokines up- 5.  CSF levels of SP and NG factor serotonin, NE dopaminergic regulated (IL10, and  levels of serotonin, GABA, system expression 3.Abnormal central pain IL25, IL36A) NE. processing 3. Granulocyte-specific genes are down-regulated ( FCER1A, MS4A2, CPA3) abnormal pain processing normal Primary afferent NK-1

AMPA Pain neuron Release of EAA/ SP NMDA receptor Quiet glia

fibromyalgia Primary afferent NK-1

Pain neuron AMPA Enhanced release EAA /SP

NMDA receptor Activated glia

Adapted from Bradley LA. Pathophysiology of Fibromyalgia. Am J Med 2009 genetic signature

Genes Mechanism -X 8.5 risk in 1° relatives COMT Catecholamine metabolism -Differential RNA expression of ADRB2 (β2 adrenergic Altered sympathetic activity 421 genes identified in 70 receptor) patients and 70 controls HTR2A( serotonin Altered serotoninergic function receptor 2A) -Changes in gene expression and D4 polymorphism Altered dopaminergic function concentrations of microRNAs TAAR1 Modulates dopaminergic receptor -Expression signatures for fibromyalgia with 10 candidate CNR1 Cannabinoid receptor genes  sensitivity 95% and RGS4 Protein G signaling specificity 96% Adapted from Ablin JN et al 2015 fMRI in fibromyalgia Comparison effects of similar pain intensity in patients and controls

Arthritis & Rheumatism Volume 46, Issue 5, pages 1333-1343, 8 MAY 2002 DOI: 10.1002/art.1022 http://onlinelibrary.wiley.com/doi/10.1002/art.10225/full#fig2 fMRI in fibromyalgia Comparison effects of similar stimulus pressures in patients and controls

Arthritis & Rheumatism Volume 46, Issue 5, pages 1333-1343, 8 MAY 2002 DOI: 10.1002/art.10225http://onlinelibrary.wiley.com/doi/10.1002/art.10225/full#fig3 environmental triggers

• Infections (Epstein-Barr virus, Lyme disease, Q fever, hepatitis)

• Physical trauma (motor vehicle collisions)

• Psychological trauma ( deployment/ abuse/death / sexual )

therapeutic framework

Education

Collaboration

Treatment

Focus on progress interdisciplinary management Grade A evidence : • cognitive-behavioral therapy (CBT) • Aerobic exercise / PT • CAM therapies Opioids • EMG biofeedback / Neuro-feedback TPI BDZ Grade B evidence: • Pharmacotherapy Marijuan • Acceptance /commitment group therapy • Educational interventions a

Grade C evidence: • Mindfulness FDA approved pharmacotherapy

Pregablin Milnacipran Duloxetine

Binds presynaptic calcium Inhibits NE reuptake Selective inhibition of channels  decreases serotonin and NE reuptake glutamate, NE, SP 50 mg bid to 150 mg TID 12.5 mg QD to 50 mg BID 30 mg QD to 60 mg QD

Meta-analysis-3 RCT n=1890 15-wk DBRCT n=1196 patients DBRCT n=588 patients reduces pain and improves 27-wk RCT n= 888 patients reduces pain severity and function Improves pain, fatigue and interference with quality of function. life summary

• Fibromyalgia is a prototypical centralized pain syndrome

• There is no agreed-upon FM phenotype or the exact mechanisms driving its multifactorial pathogenesis.

• Both genetic and environmental triggers involved in development of fibromyalgia with changes in the pain matrix.

• Management requires an interdisciplinary approach and collaboration.  Be able to accurately diagnose fibromyalgia

Understand the pathomechanism of fibromyalgia

 Identify a multimodal treatment plan for patients with fibromyalgia